Two unrelated patients are reported: one with isolated familial asplenia diagnosed postmortem, the other with isolated hyposplenism diagnosed after recurring invasive bacterial infections. Because both children died of fulminant septic shock, the importance of early diagnosis of splenic dysfunction is evident. Clues for an early diagnosis of congenital asplenia are recurrent invasive bacterial infections, Howell-Jolly bodies in the blood smear or a relative with congenital isolated asplenia. Although the guidelines for infection prevention in asplenism--patient education, antibiotic prophylaxis and vaccination--are well defined, controversy remains as to how to differentiate hyposplenism from functional asplenism. Conclusion: Based on the present observations, we define a patient as functionally asplenic--and therefore at risk for life-threatening infections-when Howell-Jolly bodies are present in the blood smear, a very small spleen is found by ultrasound, or splenic blood flow is compromised.